tbuckley/cabot-search huggingface dataset:
Novel algorithm for assigning risk/disease-directed treatment (DDT) choice in locally advanced primary squamous cell carcinoma head and neck (SCCHN): Using pretreatment data only.
Authors: Eyal Talor, Philip T Lavin, Dusan Markovic
Journal: Journal of Clinical Oncology (2022)

e18070 Background: Locally advanced primary SCCHN, DDT options (radiotherapy (RTx) or concurrent Chemoradiotherapy (CRTx)) is performed only following surgery (National Comprehensive Cancer Network [NCCN] Guidelines). A novel 2-step exclusion algorithm was developed, based only on N classification and imaging (CT; MRI +/- PET) to detect clinical features only from screening/entry findings. The algorithm was developed using the IT-MATTERS SCCHN pivotal study (Clinical trials.gov NCT01265849) data to identify treatment naïve lower risk (LR) for recurrence subjects receiving neoadjuvant immunotherapy prior to surgery to optimize long-term overall survival (OS). Methods: SCCHN patients are routinely examined and imaged at entry/screening to establish TNM classification and disease stage. Imaging is performed using CT, MRI, and/or PET-CT/PET-MRI per NCCN Guidelines. These imaging techniques can reliably detect extracapsular cervical lymph node spread before surgery, allowing the algorithm to be constructed and validated. Algorithm rules target CRTx bound (“High-Risk”) patients leaving RTx bound (“Low-Risk”) locally advanced primary disease patients at entry. The 2-step exclusions are: (1) exclude all N2 leaving only those with N0-N1, (2) further exclude those exhibiting extra capsular spread (PET-CT or PET-MRI). We retained those determined by study physicians to receive CRTx for the algorithm validation exercise only. The n = 923 pivotal study intent to treat (ITT) population was used to validate the algorithm. Results: Overall algorithm coverage was 99.9% (922/923 ITT except one missing N case) with 24.6% having N2 and 75.3% N0/N1. Among algorithm exclusions, 81.3% (282/347) were High-Risk; among algorithm inclusions, 60.6% (349/576) were Low-Risk. Algorithm validation: Among all Low-Risk cases in the study (n = 380), 91.8% (349/380) met the algorithm criteria; among all High-Risk cases, 60.4% (282/467) were correctly excluded by the algorithm. Remaining were physician choice. Overall, algorithm alone predicted 74.5% (631/847) risk group (combined low and high) accurately. Significant OS advantage (2-sided log rank p = 0.0376) to Immunotherapy regimen + standard of care (SOC) surgery + RTx vs SOC alone was seen for Low-Risk cases selected only by the 2-step algorithm. Conclusions: The algorithm provided near perfect (99.9%) ITT population coverage, achieved near 75% overall accuracy, with 91.8% accurate predictive value for the low-risk group demonstrating significant OS. Thus, risk group can be inferred at screening consistent with clinical practice and NCCN Guidelines. The algorithm can be used to help identify low risk SCCHN patients at entry to receive neoadjuvant immunotherapy before surgery.
Trends in Medicare oral anticancer drug utilization among relapsed and refractory chronic myeloid leukemia patients.
Authors: Kaitlyn McBride, Sophie Snyder
Journal: Journal of Clinical Oncology (2022)

e19058 Background: The treatment landscape for patients with relapsed and refractory (RR) chronic myeloid leukemia (CML) has changed significantly in recent years, with the introduction of targeted oral anticancer therapies. Current guidelines from the National Cancer Comprehensive Network (NCCN) recommend tyrosine-kinase inhibitors (TKIs) for second line and subsequent therapy. Recent real-world data evaluating treatment patterns in RR CML is limited. Study objective was to evaluate treatment patterns and trends in utilization of oral anticancer agents among Medicare beneficiaries diagnosed with RR CML, from 2017-2019. Methods: Retrospective study using Medicare Part D Prescription Drug Event Files, which contain records on prescription drug fills among Medicare beneficiaries enrolled in Fee-for-Service and Medicare Advantage plans. Beneficiaries diagnosed with RR CML (C9212 ICD-10) and prescribed oral anti-cancer therapy (Bosutinib, Dasatanib, Nilotinib, Ponatinib or Imatinib Mesylate) were identified and followed for at least 12 months, from index diagnosis until end of study period (December 31, 2019) or death. Trends in utilization by oral therapy, by number of beneficiary utilizers and prescription drug claims, were evaluated from 2017 to 2019. Results: Overall, 327 Medicare beneficiaries with a diagnosis of RR MM were prescribed an oral TKI therapy (Bosutinib, Dasatanib, Nilotinib, Ponatinib or Imatinib Mesylate) throughout the study period (2017-2019). The number of beneficiaries prescribed at least 1 oral therapy increased between 2017 and 2019, from 154 to 212 (Table). Total utilization also increased: from 210 prescription drug claims in 2017 to 296 in 2019. Throughout the study period, Imatinib Mesylate had the largest market share among all oral therapies, however the share decreased over time (from 35.7% in 2017 to 30.7% in 2019). Nilotinib had the largest gain in market share during this period, from 15.7% to 20.9%. Conclusions: Study findings suggest utilization of oral therapies are increasing over time, and shifting from Imatinib Mesylate to newer therapeutic agents. Given the high costs for these novel therapies, future research should examine trends in patient out-of-pocket spending, as well as factors impacting patient adherence.[Table: see text]
Challenges and outcomes of treating acute myeloid leukemia (AML) in resource-constrained settings.
Authors: Sri Krishna Sahitya Srikrishna Dangudubiyyam, Rishi Dhawan, Anusha Swaminathan, Pragna Stitha, Ramavath Devendra Naik, Mukul Aggarwal, Pradeep Kumar, Jasmita Dass, Ganesh Viswanathan, Seema Tyagi, Tulika Seth, Manoranjan Mahapatra
Journal: Journal of Clinical Oncology (2022)

7014 Background: Acute myeloid leukemia (AML) is a heterogeneous disease. Improvement in supportive care, has considerably improved AML induction outcomes, decreasing induction deaths to &lt;5% in recent studies. However, induction deaths during AML treatment in resource constraint settings remains as high as 25% in young adults. In this study we explore various challenges encountered in treating AML patients in one of the largest public sector teaching hospitals in India. Methods: Consecutive patients diagnosed with AML and registered in our clinic from January 1, 2018 to December 31, 2019, were included. Results: Of 316 patients diagnosed with AML, only 181 (57%) were able to get admitted to our institute for remission induction treatment. Median time from diagnosis to treatment initiation was 9.5 days (range, 0-232 days). Almost half (N=88; 49%) of admitted patients had infections at the time of admission. Among these, 31 (35%) had invasive fungal infection; 14 possible, 15 probable, and 2 proven. Fifty-two (29%) patients died prior to starting their remission induction therapy. Induction mortality in our cohort is 40%. Primary induction failure and primary refractory disease were noted in twenty (18%), and 5 (4%) patients respectively. Only 1 patient was able to get all three high dose cytarabine (HIDAC) consolidations on time. Median time to first HIDAC was 39.5 days (range, 28-91). Of 83 patients who were candidates for consolidative allogeneic hematopoietic cell transplantation (HCT), only ten (12%) patients were able to get transplanted. Median time to HCT from CR1 was 3.8 months (range, 1.89-12.8). The median event free survival (EFS) was 1.7 months (95%CI, 1.03-2.5) and median overall survival was 2.5 months (95%CI, 1.6-3.6). The median EFS in favourable risk, intermediate risk and adverse risk AML was 3.6 months, 3.7 months, and 3.4 months respectively. Likewise the median OS was 8.8 months, 11.8 months and 7.4 months in the three risk strata respectively. Conclusions: Outcomes of AML treatment in our cohort are discordant with that reported from the West. Our study identifies various challenges in treating AML in resource-constraint setting. Strategies need to be formulated to overcome these challenges. [Table: see text]
Dose-dependent efficacy of bevacizumab in recurrent glioblastoma.
Authors: Jawad Melhem, Ali Tahir, Eirena Calabrese, Inga Granovskaya, Eshetu G. Atenafu, Arjun Sahgal, Mary Jane Lim-Fat, James R. Perry
Journal: Journal of Clinical Oncology (2022)

e14042 Background: Bevacizumab (bev), at a standard dose of 10 mg/kg every 2 weeks is associated with prolonged progression free survival (PFS) but no improvement in overall survival (OS) in recurrent glioblastoma (rGBM). While there are reports of lower dose regimens of bev being better tolerated and effective in rGBM, this has not been studied in comparison to a standard dose of bev. The main aim of this study is to report on the dose-dependent efficacy of bev by comparing PFS and OS in rGBM patients receiving standard dose (SD) vs lower dose (LD) of bev. Methods: A single-center retrospective study of patients with rGBM started on bev between 2015 – 2020 was performed. Clinical and treatment data including bev dose regimen (SD [10 mg/kg every 2 weeks] vs LD [5 mg/kg every 2-3 weeks or 10 mg/kg every 3 weeks]) received at the time of rGBM diagnosis were captured. Overall survival (OS) and progression-free survival (PFS) on bev were compared between the two groups using the Kaplan-Meier product-limit method. Log-rank test was used to compare potential predictive factors. Cox regression model was performed for multivariable analysis of OS and PFS. Results: A total of 96 patients were included with a median follow-up duration of 6.84 months (range 1.12-50.63 months) from date of the first infusion. The LD group consisted of 55/96 patients (57 %) and the age in the LD group was significantly older than the SD group (62 vs 54 years p = 0.009). There was no significant difference in MGMT status between the 2 groups (p = 0.73). Eight patients received lomustine with bev (3 from the standard and 5 from the low dose group). The LD group had prolonged OS (10.23 months versus 6.28 months; p-value = 0.0010) and PFS (5.89 months versus 3.22 months; p-value = 0.0112). Multivariable analysis including dose of bev, extent of resection, gender and age revealed that standard dose of bev, subtotal resection and female sex were associated with worse OS. Eleven patients in the SD group vs 15 patients in the LD group reported an adverse event related to bev. Conclusions: In this study we demonstrate that a reduced dose of bev (5 mg every 2-3 weeks) prolonged both the OS and PFS compared to a standard dose of 10 mg/kg every 2 weeks. This may represent a better and more cost-effective option for patients with rGBM in need of salvage therapy.
Novel predictors associated with therapeutic effects of immune checkpoint inhibitors on bone metastasis of non-small cell lung cancer.
Authors: Yohei Asano, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi, Shinji Miwa, Kentaro Igarashi, Hirotaka Yonezawa, Sei Morinaga, Shiro Saito, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2022)

e21071 Background: In recent years, immune checkpoint inhibitors (ICIs) have brought dramatic therapeutic effects on lung cancer. However, there are few reports regarding the therapeutic effect of ICIs on bone metastasis of non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the therapeutic effects of ICIs on bone metastases of NSCLC and to analyze the predictors associated with ICI's response to them. Methods: This retrospective study analyzed NSCLC with bone metastases who initiated ICI treatment between 2016 and 2019. Clinical data was investigated and used as variables for analyzing the therapeutic effect predictors of ICIs. Blood sampling data were used within 1 week before ICI treatment initiation. The therapeutic effect of ICIs on bone metastases was evaluated by MD Anderson criteria (MDA criteria), and overall survival (OS) after the initiation of ICI treatment was investigated. Based on the evaluation of MDA criteria, univariate analysis was performed between the response group (CR+PR) and non-response group (SD+PD), and variables with p &lt; 0.05 were used for multivariate logistic regression analysis to investigate the predictors associated with the therapeutic effect of ICIs. Results: The 55 patients were included comprising 40 males and 15 females (mean age of 66.3±7.9 years) and the mean follow-up period was 23.2 months. The response rate of ICIs to bone metastasis was 30.9% including 3 cases in CR and 14 cases in PR. The median survival time was 9.3 months, and the 1-year and 2-year survival rates were 40.6% and 19.3%, respectively. The OS was significantly longer in the response group than in the non-response group (p &lt; 0.01). In the blood sampling data, the cutoff value of neutrophil-to-lymphocyte ratio (NLR) determined by receiver operating characteristic (ROC) curve analysis was 2.1. The multivariate analysis based on the variables with p &lt; 0.05 in the univariate analysis revealed significant differences in sex, treatment line of ICIs, and NLR (Table). Conclusions: Treatment with ICIs showed favorable responses to bone metastasis and better prognosis in advanced NSCLC. Moreover, this study revealed that “female, NLR &lt; 2.1, and first-line treatment of ICIs” were independent predictors associated with favorable response to bone metastasis.[Table: see text]
Melanoma of unknown primary: Favorable survival persists in the immunotherapy era.
Authors: Satish Maharaj, Nikita Jain, Anas Albawaliz, Donald M. Miller, Jason Alan Chesney
Journal: Journal of Clinical Oncology (2022)

e21513 Background: Patients with advanced melanoma have historically had better survival in those with unknown primary (MUP) than known primary (MKP). Trends in survival since the introduction of immunotherapy have not been established. Methods: We conducted a retrospective cohort study of patients with advanced/metastatic melanoma (Stage IIIC/IV disease) treated during the period 2014-2020 at the University of Louisville. The primary outcome was overall survival in MUP compared with MKP. Differences in clinical characteristics, BRAF status, tumor mutational burden and PD-L1 tumor proportion score (Dako 22C3 assay) were examined. Differences between numerical variables were calculated based on parametric or non-parametric comparisons accordingly and categorical data analyzed using chi-squared testing. Kaplan-Meier survival analyses were performed with log-rank testing to evaluate differences. Alpha was set at 0.05 for significance. Results: Of the 79 patients with advanced/metastatic melanoma included, 12 had MUP and 67 had MKP. Of those with MKP, the primary site was cutaneous melanoma in 65 and anal melanoma in 2. Clinical characteristics showed the majority were male, with median age of 61 years. There were no significant differences in demographics, distribution of stage, BRAF status, TMB, PDL-1 score or treatment modality between MUP and MKP groups (Table). The median follow-up time overall was 50 months. The MUP group demonstrated significantly better survival with 3-year OS of 92% vs. 62% in MKP, and 5-year OS of 83% vs 44% in MKP. Median survival was 54 months for MKP and not reached for MUP. For MKP, the 5-year OS of 44% compares similarly to other cohorts. The Keynote-001 trial of advanced/metastatic melanoma treated with pembrolizumab reported 5-year OS of 41%. This is approximately a 4-fold improvement compared to cohorts treated before the approval of immunotherapy, where the 5-year OS was in the range of 10% [Lee et al, 2009]. The 5-year OS for metastatic MUP was previously in the range of 18%, also suggesting improvement by about 4-fold with the use of immunotherapy. Conclusions: Melanomas of unknown primary continue to have better survival with durable response on immunotherapy even in the advanced/metastatic setting. The exact mechanisms for this survival advantage remain unknown but are likely immune-mediated.[Table: see text]
Clinical utility of widespread germline testing of cancer patients in a diverse community cancer clinic.
Authors: Kashyap B. Patel, William K. Oh, Tomi Jun, Sashi Naidu, Nyati Nathwani, Gabriel Hansen, Adara Hubert, Hirangi Mukhi, Shilpa Chhadwa, Valerie Zabala, Sonia Gill, Randall Branchcomb, Dhwani Mehta, Sandra Nixon, Ashima Kodali, Michelle Zimmerman
Journal: Journal of Clinical Oncology (2022)

e18537 Background: Identification of germline mutations can determine prognosis, inform targeted therapies, allow risk-reducing interventions, and suggest additional cancer screenings in patients and their biological relatives. Large prospective cohort studies have been historically skewed towards wealthier socioeconomic populations that lack ethnic diversity and vastly underrepresent African Americans. Recently, small studies outside of standard clinical guidelines reveal detection of pathogenic variants in germline testing with significant clinical ramifications. We present our single center experience of prospective germline testing in a small community clinic in suburban and rural South Carolina with understudied real-world populations. Methods: We performed germline testing, outside of guidelines, in patients presenting at earlier age or with either rare tumors, or recurrent/multiple malignancies. This prospective, observational cohort included a suburban and rural underserved population where approximately 30% identify as African American. Patients were counselled about testing that performed outside of guidelines. Results: We identified 67 individuals outside the guidelines concordance, compromising of 45 male and 22 female patients, within the first 6 months of this prospective, observational cohort. Patients reported race as African American (14), White (50), or Asian American (3). Rare germline findings included Li Fraumeni syndrome, Fanconi’s syndrome, Perelman’s disease, and Von Hippel Lindau’s disease. We summarize our findings in the attached table. Conclusions: There are limited studies that report prevalence of germline findings in cancer patients who are unselected by clinical practice guidelines. Studies also lack representation of ethnic minorities. Recently published data on the clinical utility of broad-based germline testing of all incoming patients suggest current practice of guidelines and genetic counselor recommended testing should be re-examined for broader testing for all incoming cancer patients in a more inclusive manner.[Table: see text]
Genomic landscape and homologous recombination repair (HRR) genes analysis in Chinese prostate cancer (PCa) patients.
Authors: Jianhua Liu, Jiantang Lu, Jian Wang, Yuan Hu, Binbin Li, Xuefeng Zhong, Mengli Huang
Journal: Journal of Clinical Oncology (2022)

e17020 Background: HRR gene mutations have been proven to be effective biomarkers for PARP inhibitor (PARPi) therapy in metastatic castration resistant PCa. The epidemiological data of genomic variation and the characteristic of HRR gene alterations in Chinese population is still insufficient. Methods: Tumor tissue samples (including surgical and biopsy samples) and blood samples from 250 pathologically confirmed PCa patients were collected and analyzed using next generation sequencing (733-gene panel). Tumor mutation burden (TMB) was defined as total number of somatic non-synonymous mutations in coding region. Homologous recombination deficiency (HRD) was evaluated by the sum of the loss of heterozygosity, telomeric allelic imbalance and large-scale state transition. Somatic or germline alterations (including copy number reduction, CNV-loss) of HRR pathway genes were classified as HRR-altered positive. Results: In total, the top three alteration frequency somatic genes were FOXA1 (24.9%), TP53 (15.2%) and MYC (13.6%) while the top three alteration frequency germline genes were DPYD (17.1%), UGT1A1 (13.2%) and SLX4 (4.3%). In HRR pathway genes, the top three alteration frequency somatic genes were CDK12 (9.7%), ATM (4.7%) and BRCA2 (3.9%) while the top three alteration frequency germline genes were BRCA2 (3.1%), PALB2 (1.9%) and BRCA1 (1.6%). 25.6% (64/250) cases carried HRR gene alterations. Among HRR-altered positive cases with HRD score, only 8.9% (4/45) carried more than one HRR gene alteration and most carried a single HRR gene alteration (40.0% [18/45] in CDK12, 17.8% [8/45] in ATM or BRCA2, 11.1% [5/45] in BRCA1 and 2.2% [1/45] in PALB2 or FANCA). 61 HRR gene alterations were detected in these 45 cases and the commonly alteration types of HRR genes were single base substitution (47.5%, 29/61). The alteration type of CNV-loss (14.8%, 9/61) was only detected in somatic samples. The HRD score of HRR-altered group was significantly higher than wild group (median HRD socre, altered-type vs. wild-type = 23.5 vs. 19.0, P= 0.0097). And there was no significant difference in HRD score between CNV-loss and other alteration types. Moveover, the TMB level of HRR-altered group tended to be higher than wild group (median TMB, altered-type vs. wild-type = 4.5 vs. 2.8 Muts/Mb, P= 0.5). Conclusions: The results illustrated the molecular characteristics of HRR gene in Chinese PCa and indicated that HRR gene alterations (including CNV-loss) were associated with higher HRD score. These data provide further evidence for the clinical management of PARPi personalized therapy.